The Eaton-Lambert syndrome (ELS) is a defect of neuromuscular transmission, frequently associated with carcinoma of the lung, especially that of small-cell tyep. As in myasthenia gravis, the disease is characterized by a specific functional abnormality suggesting that the motor nerve terminals release nor mobilize the normal number of acetylcholine (ACH) quanta in response to a nerve impulse. The etiology and pathogenesis of ELS are unknown. The mechanism underlying the deficient release of transmitter quanta has not been demonstrated. No explanation is yet available for the apparent relationship between the syndrome and the presence of neoplasm. However, the high incidence of the disease with the specific type of neoplasm strongly suggests an etiological significance. The objective of the proposed of the proposed study is to verify the two hypotheses: (I) circulating normal factors are implicatd in the presynaptic blockade of neuromuscular transmission that characterizes ELS and (II) the neoplastic form of the disease is caused by an autoimmune mechanism which triggers the production of autoantibodies to a arcinomatous antigen which react with an antigenic factor on the motor nerve terminal, producing the presynaptic transmission defect. With the aim of verifying these hypotheses, experiments will be carried out to (1) determine the in vitro neuromuscular blocking action of serum factors of patients with ELS and those with pathologically confirmed small-cell carcinoma of the lung; (2) further explore the range of pre- and postjunctional abnormalities in intercostal muscle biopsies of patients with ELS and small-cell carcinoma; (3) passively transfer the transmission defect in ELS to the recipient animals by injecting serum factors or tumor tissue extracts of the patients; and (4) develop an animal model of the disease by immunizing with ELS tumor tissue extracts. The research techniques involved in this investigation include conuentional electrophysiologic techniques for intracellular recording, evoked potential electromyography, indiction of autoimmune responses, and gel-filtration chromatography.